Hereditary Syndromes Manifesting as Endometrial Carcinoma: How Can Pathological Features Aid Risk Assessment?
Table 3
Endometrial carcinoma testing result using MSI analysis and/or immunohistochemistry with additional testing strategies for Lynch Syndrome. Additional suggested testing strategies for patients who have been tested using either MSI analysis and/or immunohistochemistry with a four-panel marker (MHL1, MSH2, MSH6, and PMS2) or a #two-panel marker (MSH6 and PMS2) (adapted from [43]).
MSI analysis
Immunohistochemistry protein expression
Possible causes
Further action
MLH1
MSH2
MSH6#
PMS2#
MSS/MSI-L
+
+
+
+
Sporadic carcinoma
None.
MSI-H
+
+
+
+
Germline mutation in MMR or EPCAM genes
MLH1, MSH2, then MSH6, PMS2, and EPCAM genetic testing
MSI-H
NA
NA
NA
NA
Sporadic or germline mutation in the MMR or EPCAM genes
Consider IHC to guide germline testing if IHC is not done germline testing of MLH1, MSH2, MSH6, PMS2, and EPCAM genes
MSI-H or NA
−
+
+
−
Sporadic cancer or germline mutation of MLH1
MLH1 promoter methylation testing. MLH1 genetic testing if absent hypermethylation or if testing not done
MSI-H or NA
−
+
+
+
Germline mutation MLH1
MLH1 genetic testing
MSI-H or NA
+
+
+
−
Germline mutation of PMS2, rarely MLH1
PMS2 genetic testing if negative MLH1 testing
MSI-H or NA
+
−
−
+
Germline mutation of MSH2 or EPCAM, rarely of MSH6
MSH2 genetic testing, if negative EPCAM, if negative MSH6
MSI-H or NA
+
−
+
+
Germline mutation of MSH2
MSH2 genetic testing if negative EPCAM testing
MSI-H, MSI-L or MSS
+
+
−
+
Germline mutation of MSH6, less likely MSH2
MSH2 genetic testing if negative MSH6 testing
MSI-L, microsatellite low; MSI, microsatellite high; MMR, mismatch repair genes (i.e., MLH1, MSH2, MSH6, and PMS2); NA, not available; +, protein expression present in tissue; and −, protein expression not present in tissue.
